Mlca2^DBA/2J
QTL Variant Detail

Summary

• QTL variant: Mlca2^DBA/2J
• Name: modifier of locomotor activity 2; DBA/2J
• MGI ID: MGI:3701689
• Synonyms: 98D1
• QTL: Mlca2 Location: unknown Genetic Position: Chr4, Syntenic

Variant origin

• Strain of Specimen: DBA/2J

Variant description

• Allele Type: QTL
• Mutation: Undefined
• This allele confers increased spontaneous locomotor activity compared to C57BL/6J. (J:118059)
• Inheritance: Semidominant

Notes

Original DBA/2J male founders were ENU-mutagenized. This allele is presumably the result of induced-mutation.

Mapping and Phenotype information for this QTL, its variants and associated markers

J:118059

Genetic loci modifying dopaminergic homeostasis in C57BL/6J-Slc6a3^tm1Mca mice were mapped using crosses with ENU-mutagenized DBA/2J males. G1 mutagenized DBA/2J mice were crossed to C57BL/6J-Slc6a3^tm1Mca. Progeny derived from three G2 founder mice with increased locomotor phenotype were used for linkage analysis. Genome scan was performed using 99-117 microsatellite markers. Parental strain C57BL/6J-Slc6a3^tm1Mca displays significantly increased spontaneous locomotor activity compared to wild type C57BL/6J. Animals were tested by monitoring locomotor activity over a period of 2 hours.

Linkage to locomotor activity was detected at 38.3 cM on mouse Chromosome 2 (LOD=3.7). The broad QTL interval (30 cM - 80 cM) suggests more than one QTL may be present. This locus is designated Mlca1 (modifier of locomotor activity 1). A mutant DBA/2J-derived allele at Mlca1 appears to confer increased spontaneous locomotor activity with semidominant inheritance and the effect is independent of Slc6a3^tm1Mca.

Linkage to increased locomotor activity was also detected and confirmed at 67.5 cM on mouse Chromosome 4 (LOD=3.5). This locus is designated Mlca2 (modifier of locomotor activity 2). A mutant DBA/3J-derived allele at Mlca2 appears to enhance locomotor activity with semidominant inheritance and is independent of Slc6a3^tm1Mca status.

A major semidominant locus was detected at 49.5 cM on mouse Chromosome 12 (LOD=7.2) in 2 of the founder lines. This locus is designated Mlca3 (modifier of locomotor activity 3). The QTL interval spans approximately 40 cM - 60 cM. A mutant DBA/2J-derived allele at Msla3 appears to confer increased locomotor activity with semidominant inheritance. The effect does not dependent on the presence of the Slc6a3^tm1Mca mutation.

Increased locomotor activity in Slc6a3^tm1Mca heterozygous progeny mapped to 36.8 cM on mouse Chromosome 16 (LOD=2.9). This locus is designated Mlca4 (modifier of locomotor activity 4). C57BL/6J-derived alleles at Mlca4 enhance locomotor activity in Slc6a3^tm1Mca heterozygous animals.

On mouse Chromosome 18, a locus at 33.5 cM exhibits linkage to locomotor activity in Slc6a3^tm1Mca heterozygous progeny (LOD=2.5). This locus is designated Mlca5 (modifier of locomotor activity 5). A mutant DBA/2J allele at Mlca5 appears to enhance locomotor activity in Slc6a3^tm1Mca heterozygous animals.

References

• Original: J:118059 Speca DJ, et al., A genetic screen for behavioral mutations that perturb dopaminergic homeostasis in mice. Genes Brain Behav. 2006 Feb;5(1):19-28
• All: 1 reference(s)